Inhibitory effects of Japanese apricot (Prunus mume Siebold et Zucc.; Ume) on Helicobacter pylori-related chronic gastritis.

OBJECTIVES: We investigated the correlation between Japanese apricot (JA) intake and Helicobacter pylori-related chronic atrophic gastritis (CAG). METHODS: A questionnaire was administered and serum anti-H. pylori IgG antibodies measured in 1358 asymptomatic adults. The subjects were divided into high-intake and low-intake groups. Histological and serological evaluation of H. pylori-related CAG was performed in 68 non-elderly volunteers. RESULTS: The H. pylori-negative rate did not differ significantly between the high-intake and low-intake groups. Mean antibody titers were lower in the high-intake group, but the difference was not significant. There was no significant difference in the rate of H. pylori infection on the basis of JA intake when subjects were stratified by age. Among H. pylori-positive non-elderly subjects, antibody titers were significantly lower in the high-intake group (P=0.041). Endoscopic tissue biopsy from the 68 volunteers showed less H. pylori bacterial load and mononuclear infiltration irrespective of gastric site in the high-intake group. In the high-intake group, antral neutrophil infiltration was significantly less pronounced and corporal atrophy was less extensive. Serological evaluation using serum PG levels also confirmed these histopathological data. CONCLUSIONS: Our findings strongly indicate a preventive effect of JA intake on CAG by inhibiting H. pylori infection and reducing active mucosal inflammation.

Promotive effects of hyperthermia on the cytostatic activity to Ehrlich ascites tumor cells by diverse delta-alkyllactones.

AIM: To evaluate promotive effects of hyperthermia on antitumor activity of new delta-alkyllactones (DALs) of low molecular weight (184-254 Da), chemically synthesized, which are different from natural macrocyclic lactones of high molecular weight (348-439 Da), such as camptothecin and sultriecin. METHODS: A suspension of Ehrlich ascites tumor (EAT) cells was mixed with a DAL in a glass tube, heated at 37 or 42 degrees C for 30 min in a water bath, and cultured at 37 degrees C for 20 or 72 h. Cell viability was measured by the mitochondrial dehydrogenase- based WST-1 assay. DALs incorporated into EAT cells was extracted and measured by gas-liquid chromatography. RESULTS: The reduction of cell viability by DALs was markedly enhanced upon the treatment at 42 degrees C compared to that at 37 degrees C. At 37 degrees C, delta-hexadecalactone (DH16:0) and delta-tetradecalactone (DTe14:0) displayed cytostatic activity (at 100 microM survival level: 20.7%, 66.1%; at 50 microM--41.2%, 82.4%, respectively). Their activity was more marked at 42 degrees C (at 100 microM 10.6%, 27.6%; at 50 microM 30.6, 37.5%, ibid). The other DALs, delta-undecalactone (DU11:0), delta-dodecalactone (DD12:0), and delta-tridecanolactone (DTr13:0) were almost ineffective. Evaluation of survival rate in the cells treated for 30 min by DALs with the next culturing of EAT cells for 72 h resulted in the enhanced carcinostatic activity of DH16:0 and DTe14:0 even at concentrations as low as 25 microM at either 37 degrees C (18.5%, 78.5%, ibid) or 42 degrees C (5.0%, 42.0%, ibid), but the others exhibited slight activity or none. DH16:0 was effective at either 37 degrees C (36.0%) or 42 degrees C (23.0%) even at a lower dose of 10 microM. At the same time only the most cytostatic DH16:0 was incorporated into EAT cells and the rate of incorporation was more at 42 degrees C than at 37 degrees C. CONCLUSION: Delta-hexadecanolactone (DH16:0) exhibited the most cytostatic effect that was significantly enhanced by hyperthermia. It allows to consider it as a potent antitumor agent, especially in combination with hyperthermia.

Biochemical markers of bone turnover and bone loss at the lumbar spine and femoral neck: the Taiji study.

The purpose of this study was to ascertain whether biochemical markers of bone turnover predict bone loss. The survey was carried out in Taiji, Wakayama Prefecture, Japan. From a list of inhabitants aged 40-79 years, 400 participants (50 men and 50 women in each of four age groups) were selected randomly. Bone mineral density (BMD) was measured, and blood and urine samples of all participants were examined to obtain values for eight biochemical markers: alkaline phosphatase (ALP), bone Gla protein (BGP), type I procollagen (carboxyterminal peptide of type I procollagen; PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP), and urinary excretion of calcium (Ca), phosphate (P), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr). Each marker was evaluated as a predictor of the rate of bone change in lumbar spine and femoral neck BMD over a 3-year period. The value of Pyr was significantly related to the change of lumbar spine BMD in men (P = 0.009), and that of BGP was found to be significant in women (P = 0.045). By contrast, none of the bone markers significantly correlated with bone loss at the femoral neck. The coefficient of determination at the lumbar spine was 5% and 7% at the femoral neck only. We conclude that biochemical markers of bone turnover cannot predict bone loss rates in middle-aged or elderly Japanese men and women over a 3-year period with sufficient accuracy for use in clinical decision making.

[Pneumonitis induced by the drug ougon].

We report a case of drug-induced pneumonitis associated with the herbal medications Sho-saiko-to and Ouren-gedoku-to. A 62-year-old man experienced fever and dry cough after using Ouren-gedoku-to for 2 months. He was admitted to our hospital because a subsequent 5-day course of Sho-saiko-to for suspected bronchitis aggravated these symptoms and caused exertional dyspnea. Chest X-ray films revealed a ground-glass appearance in both lower lung fields. Cessation of these medications improved the patient's clinical and X-ray findings. Bronchoalveolar lavage showed an increase in lymphocytes with a decreased CD 4/CD 8 ratio. While drug-induced lymphocyte stimulation tests gave negative results, challenge tests for Ouren-gedoku-to and Sho-saiko-to were both positive. A diagnosis of drug-induced pneumonitis was made. Our findings suggested the involvement of Ougon, the only common ingredient in the two medications.

Inhibitory effect of TNP-470 on experimental choroidal neovascularization in a rat model.

PURPOSE: To determine whether an angiogenic inhibitor, TNP- 470 (TNP), an analogue of fumagillin, inhibits choroidal neovascularization (CNV) induced by diode laser photocoagulation in a rat experimental model. METHODS: Fundus laser photocoagulation was performed on Brown Norway rats to induce CNV. In the treatment group, TNP was administered intraperitoneally at the time of laser photocoagulation and on day 7 (50 mg/kg at each time). The incidence of CNV formation was evaluated by fluorescein angiography. The retina was collected from the rats on days 1, 3, 7, and 14 after laser photocoagulation, and semiquantitative polymerase chain reaction (PCR) analyses for the expression of mRNA of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were carried out. Localization of bFGF mRNA was studied by in situ reverse transcription-PCR (RT-PCR). The numbers of positively labeled cells for bFGF mRNA were compared between the TNP treatment and control groups. RESULTS: The incidence of CNV formation was 22.7% in the TNP-treated rats and that in the control rats was 61.4% (P < 0.001). The semiquantitative PCR analyses showed that bFGF mRNA was upregulated on days 3 and 7 in the control rats, but no significant changes were found in TNP-treated rats. There was no detectable difference in VEGF gene expression between the control and TNP-treated rats. bFGF mRNA was detected by in situ RT-PCR in the regenerated retinal pigment epithelial cells and cells of the outer and inner nuclear layers of the control rats. The number of positive cells for bFGF mRNA in the TNP treatment group was significantly smaller than that of the control group (P < 0.05) on days 3 and 14. CONCLUSIONS: TNP- 470 treatment reduced the incidence of laser-induced CNV formation in this experimental model. The expression of bFGF associated with CNV formation was also significantly reduced by the TNP treatment.

Steroid sulfatase expression is an independent predictor of recurrence in human breast cancer.

Steroid sulfatase (STS) hydrolyzes several sulfated steroids such as estrone sulfate, dehydroepiandrosterone sulfate, and cholesterol sulfate. In the present study, we have measured STS mRNA levels in 97 breast cancers by reverse transcription-PCR using a fluorescent primer in the presence of an internal standard RNA and evaluated its association with disease-free and overall survival. The median value was 728.0 amol/ng RNA (range, 0-11,778 amol/ng RNA). Levels were significantly higher in tumors demonstrating lymph node metastasis than in those without nodal involvement (P = 0.033) and in patients who experienced a recurrence during the follow-up period (mean, 40.8 months; median, 39 months) compared with those with no evidence of further disease (mean, 49.2 months; median, 48 months; P = 0.029). No significant associations were found between STS mRNA expression and age, menopausal status, tumor size, histological grade, estrogen receptor status, or postoperative adjuvant therapy. High levels of STS mRNA proved to be a significant predictor of reduced relapse-free survival as a continuous variable (log STS mRNA; P = 0.028). As a dichotomous variable with an optimized cutoff point of 1,240 amol/ng RNA, expression was also associated with a significantly shorter relapse-free survival rate (P = 0.002), but no significant correlation was found between the STS mRNA level and overall survival. Expression was found to be an independent factor for predicting relapse-free survival on multivariate analysis. The results thus support a putative role of STS in breast cancer growth and metastasis.

Bone loss in Great Britain and Japan: a comparative longitudinal study.

Hip fracture incidence is lower in Japan than in the West. Although differences have been found in peak bone mass and hip geometry between white and Japanese populations, these do not fully explain the difference in hip fracture rates. Variation in the rates of involutional bone loss may be an additional contributing factor. We address this issue in a prospective epidemiological study comparing bone loss rate among elderly people in Britain and Japan. Two population-based studies of bone loss rate in a British and a Japanese cohort were performed. Annual bone loss rates were obtained for 172 Hertfordshire men and 143 Hertfordshire women of mean age 66 years, and a questionnaire administered to obtain information on known confounding lifestyle factors. Eighty-six Japanese men and 90 Japanese women of mean age 69 years completed a similar study in Taiji, Japan. British men and women were heavier than Japanese men and women. Differences in lifestyle were also evident; the British men were less likely to smoke and the women more likely to consume alcohol than their Japanese counterparts. The British population also spent more time walking outdoors. Statistically significant differences between the two populations were apparent in baseline bone mineral density at lumbar spine (p < 0.05) and trochanter (p < 0.001) in men and women with Japanese subjects having lower values. There were also significant differences in bone density at the femoral neck (p < 0.001) between British and Japanese males. Men gained bone at the lumbar spine over the follow-up period in both populations. Bone loss rates were generally greater in the British female population than in Japanese women: the difference was statistically significant at the femoral neck (p < 0.05) and femoral trochanter (p < 0.001). These differences all remained significant after adjustment for differences in age between the two populations. Japanese subjects appear to have lower peak bone mass, but slower bone loss rates in later life than their European counterparts. These differences in bone loss rate help to explain the relatively low hip fracture rates found in Japan.

Determinants of bone loss in a rural Japanese community: the Taiji Study.

The objective of this study was to assess the rate of bone loss and characterize its determinants, among the inhabitants of Taiji, a rural Japanese community. A cohort of 2261 inhabitants aged 40-79 years was established using resident registration in 1992. Fifty men and 50 women in each of four age strata between 40 and 79 years were randomly selected and completed a self-administered risk factor questionnaire. Baseline bone density of lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry in 1993. BMD was measured again on the same participants in 1996. The rates of change of lumbar spine BMD in men in their 40s, 50s, 60s and 70s were 0.20%, 0.34%, 0.43% and 0.28% respectively. Rates in women were -0.35%, -1.02%, -0.10% and -0.20% respectively. At the femoral neck, rates of change in BMD among men in their 40s, 50s, 60s and 70s were 0.09%, -0.07%, 0.34% and 0.31% respectively. Femoral neck rates of change among women were -0.55%, 0.02%, 0.49% and -0.25% respectively. The rate of change of lumbar spine BMD was -0.24% in premenopausal women with regular periods, -1.99% in premenopausal women with irregular periods and -0.33% in postmenopausal women. Anthropometric measurements at baseline were also related significantly to change in bone density. Baseline weight and height were statistically significant predictors of bone loss rate. These data provide estimates of the rate of bone loss among Japanese men and women aged 40-79 years. They suggest that body build and menstrual function in women are important determinants of bone loss.

[Surgical treatment of aortic dissection (Stanford type A) using hypothermic retrograde cerebral perfusion in patients older than 70 years of age].

Since 1991, 27 consecutive patients with aortic dissection (Stanford A) have been operated on using deep hypothermic retrograde cerebral perfusion (RCP). There were no differences in ECC time (247 +/- 15 vs 307 +/- 22 min), and RCP time (47 +/- 2 vs 47 +/- 3 min) between the aged (> or = 70 y.o., n = 11) and non-aged (< 70 y.o., n = 16) group. Although the aged group showed the higher incidences of postoperative neurological complications of prolonged emergence (2 cases) and delirium (3 cases), respiratory disorder (3 cases), and renal dysfunction (3 cases), there was no significant difference in hospital mortality (18% in the aged vs 13% in the non-aged). We concluded that RCP is well acceptable procedure for surgical treatment of the aged patients with aortic dissection.

[A population survey on bone mineral density in a fishing village in Wakayama Prefecture (Part 2); The analysis of the risk factors affecting the bone mineral density].

The purpose of this study was to detect factors affecting lumbar bone mineral density (BMD) of general inhabitants in a rural community. A cohort consisting of 2261 inhabitants aged 40-79 years was set up based on the resident registration in Taiji town, Wakayama Prefecture in 1992. Fifty men and 50 women in each of four age strata (40-49, 50-59, 60-69, 70-79), totaling 400 inhabitants, were selected randomly. After completion of a questionnaire by an interviewer, items about physical characteristics such as height, body weight, wrist length and grip power were measured. Examination of BMD of the lumbar spine and proximal femur by dual energy X-ray absorptiometry was performed. Correlation coefficients between BMDs and values of physical characteristics were determined. Lumbar BMD was examined to determine whether the following factors were positive or negative: past history, alcohol consumption, smoking habit, dietary habit, exercise, and in addition, pregnancy times and menstrual status for women. Among the values of physical characteristics, body weight was the most closely correlated with lumbar BMD. The items that showed significantly high values as factors affecting lumbar BMD were a past history of diabetes mellitus (men and women in their 70s), and exercise (men in their 50s and women in their 40s). Regarding pregnancy times and menstruation, BMD in women with a history of childbirth was significantly higher than that in those without the history among the women in their 70s. Although the BMD in the women with lactation was significantly lower than that in those without it among the women in their 40s, there was no difference in BMD between the women with and without the history who were 50 years old or over. The effect of menstrual status was investigated according to years after menopause in the women in their 50s. BMD was significantly lower in the women with ar least six years after menopause than in those within five years.

[Relation between defect in comprehension and frontal lobe lesion].

We assessed anatomical findings and language defects in 14 right handed patients who had fluent aphasia following left frontal lobe lesion. From the onset of aphasia all of the patients showed fluent speech and excellent repetition but difficulty in word finding and impairment in language comprehension. We administered to all of the patients the Western Aphasia Battery, a 50-item pointing task using line drawings representing single words selected from among common Japanese words for language training for aphasics, and the Token Test. Anatomical analysis was performed using brain CT and/or MRI. The patients were divided into three groups on the basis of the extent of impairment in comprehension of single words: one group showed no impairment, another showed slight impairment and the other showed severe impairment. The lesion site differed among the groups. Each group had a different lesion site. We concluded the following: first, lesions in Brodmann's areas 6 and 9 produce impairment in comprehension of single words, with lesions extending to anterior to Broca's area producing more impairment than those without the extending lesions. Second, lesions in the frontal lobe produce impairment in comprehension of complex sentences.

Overview of effects of electrical stimulation on osteogenesis and alveolar bone.

One endpoint of periodontal therapy is to regenerate structure lost to periodontal disease. Periodontal regeneration requires both formation of a new connective tissue attachment to the tooth and formation of alveolar bone. Several procedural advances may support regeneration of the attachment, however, regeneration of alveolar bone does not occur consistently. Therefore, factors which stimulate bone repair are areas for research in periodontal reconstructive therapy. Effects of cytokines or growth factors on bone repair are examples of such areas. Another one is electrical stimulation which naturally occurs in bone, and as such bone may be particularly susceptible to electrical therapy. This overview describes the potential of electrical stimulation for bone regeneration and applications in alveolar and periodontal research.

Ferromagnetic hyperthermia in rabbit eyes using a new glass-ceramic thermoseed.

Hyperthermia is a new treatment modality to increase the tumoricidal effect of radiotherapy for choroidal melanoma. We have produced a ferromagnetic glass-ceramic composed of magnetite and wollastonite as a thermoseed for interstitial hyperthermia. The stable oxidized ceramic produced sufficient heat by hysteresis loss upon exposure to an alternating magnetic field. We studied its heat-generating properties and evaluated its possible application to ocular hyperthermia. Agar model and rabbit eye studies showed that the heat generated by the ceramic was less affected by its orientation in the magnetic field than metal alloy thermoseeds and that the retinal surface was heated to 43.5 degrees C in less than 7 min without heating the surrounding tissue. Additionally, this heating system showed a good temperature stability of +/- 0.1 degrees C under steady-state conditions without using a controller. The new glass-ceramic shows promise as a thermoseed in ocular hyperthermia.

[Hypercapnea during facial surgery under local anesthesia].

We examined the ventilation of patients whose faces were draped during facial surgery under local anesthesia. Ten patients who underwent eye surgery received hydroxyzine 25 mg and pentazocine 15 mg i.m. before local anesthesia. Arterial blood samples and end-tidal respiratory gases from nasal cannulae were collected at the following selected times: before draping their faces, 10 min, 30 min, 60 min after draping, and after the drapes were removed. Both arterial carbon dioxide tension (42 +/- 1 mmHg before draping and 46 +/- 1 mmHg at 10 min) and end-tidal carbon dioxide tension (33 +/- 2 mmHg before draping and 36 +/- 1 mmHg at 10 min) were elevated significantly after their faces were draped. Hypercapnea was completely eliminated by suctioning the expired gases. It is concluded that hypercapnea is inevitable during face or neck surgery under local anesthesia, and that the expired gases should be monitored and removed.

Breakdown of the blood-retinal barrier after radiofrequency-induced ocular hyperthermia.

To study the possible application of hyperthermia in the treatment of proliferative vitreoretinopathy (PVR), we induced hyperthermia in 15 normal rabbit eyes by a radiofrequency capacitive heating device. The retinal surface of each eye was warmed to a presumed temperature of 41 or 43 degrees C for 30 min. The thermal effect on the blood-retinal barrier (BRB) was evaluated before and 2 h after the hyperthermic regimen by means of vitreous fluorophotometry. Heat treatment to 43 degrees C at the retinal surface for 30 min increased the fluorescein leakage compared with the 41 degrees C treatment. This finding suggests that retinal hyperthermia at 43 degrees C for 30 min may cause breakdown of the BRB.

[Inhibitory effects of Hachimijiogan on micturition reflex via the locus coeruleus].

Pharmacological studies were undertaken to elucidate the role of Hachimijiogan in the micturition reflex via the locus coeruleus, using alpha-chloralose-anesthetized cats. Rhythmic contractions of the urinary bladder induced by continuous infusion of saline into the bladder were dose-dependently inhibited by intravenous injection of Hachimijiogan (10, 30 and 90 mg/kg), as well as flavoxate hydrochloride (1 and 3 mg/kg). In contrast, contraction of the urinary bladder elicited by electrical stimulation of the locus coeruleus was significantly suppressed by intravenous injection of flavoxate, but not affected by that of Hachimijiogan. These results suggest that Hachimijiogan acts on the afferent pathway from the urinary bladder to the locus coeruleus, thereby inhibiting the micturition reflex, while it has no effects on the efferent pathway from the locus coeruleus to the urinary bladder.

[A case of benign intracranial hypertension with bilateral reversible thalamic lesions on magnetic resonance imaging].

A 10-year-old girl had complained of headache, vomiting and blurred vision for one month before admission to our hospital. Her neurological findings were normal, except that the examination of the fundi revealed papilledema. The cerebrospinal fluid pressure was elevated to 220 mmH2O. The brain MRI showed bilateral and approximately symmetrical hyperintense areas located in the thalamus. These disappeared on the repeated MRI, and her symptoms regressed spontaneously within a month. Her illness was diagnosed as benign intracranial hypertension because of the favorable clinical course. These reversible thalamic lesions might be due to circulatory insufficiency associated with intracranial hypertension.